Mutations

APOE c.43+349G>A (rs61357706)

Other Names: rs61357706, APOE2269

Overview

Clinical Phenotype: Blood Lipids/Lipoproteins
Position: (GRCh38/hg38):Chr19:44907016 G>A
Position: (GRCh37/hg19):Chr19:45410273 G>A
Transcript: NM_000041; ENSG00000130203
dbSNP ID: rs61357706
Coding/Non-Coding: Non-Coding
DNA Change: Substitution
Expected RNA Consequence: Substitution
Reference Isoform: APOE Isoform 1
Genomic Region: intron 2

Findings

This intronic variant was identified in a study of 788 African Blacks and 623 non-Hispanic Whites as associated with decreased levels of LDL cholesterol in Blacks after adjusting for the common alleles APOE2 and APOE4 (β = −2.23; p = 0.0034; FDR = 0.02; Radwan et al., 2014). However, the authors noted that the association could be mediated by R163C, a variant strongly linked to c.43+349G>A (r2=1) and tied to several conditions involving altered lipid and lipoprotein profiles (Radwan et al., 2014, Pirim et al., 2019).

In the gnomAD variant database, this variant had a global frequency of 0.0056 (v2.1.1, Oct 2022). Most alleles were from carriers of African ancestry (169 of 175) and, in this group, the frequency was 0.019.

Biological Effect

The biological effect of this variant is unknown, but its PHRED-scaled CADD score (5.62), which integrates diverse information in silico, was well below 20, a commonly used threshold to predict deleteriousness (CADD v.1.6, Oct 2022).

Last Updated: 05 Dec 2022

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References

Paper Citations

  1. Radwan ZH, Wang X, Waqar F, Pirim D, Niemsiri V, Hokanson JE, Hamman RF, Bunker CH, Barmada MM, Demirci FY, Kamboh MI. Comprehensive evaluation of the association of APOE genetic variation with plasma lipoprotein traits in U.S. whites and African blacks. PLoS One. 2014;9(12):e114618. Epub 2014 Dec 12 PubMed.
  2. Pirim D, Radwan ZH, Wang X, Niemsiri V, Hokanson JE, Hamman RF, Feingold E, Bunker CH, Demirci FY, Kamboh MI. Apolipoprotein E-C1-C4-C2 gene cluster region and inter-individual variation in plasma lipoprotein levels: a comprehensive genetic association study in two ethnic groups. PLoS One. 2019;14(3):e0214060. Epub 2019 Mar 26 PubMed.

Further Reading

No Available Further Reading

Protein Diagram

Primary Papers

  1. Radwan ZH, Wang X, Waqar F, Pirim D, Niemsiri V, Hokanson JE, Hamman RF, Bunker CH, Barmada MM, Demirci FY, Kamboh MI. Comprehensive evaluation of the association of APOE genetic variation with plasma lipoprotein traits in U.S. whites and African blacks. PLoS One. 2014;9(12):e114618. Epub 2014 Dec 12 PubMed.

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